Combinatorial approaches to probe the sequence determinants of protein aggregation and amyloidogenicity

Christine Wurth, Woojin Kim, Michael H. Hecht

Research output: Contribution to journalReview articlepeer-review

13 Scopus citations

Abstract

Elucidation of the molecular determinants that drive proteins to aggregate is important both to advance our fundamental understanding of protein folding and misfolding, and as a step towards successful intervention in human disease. Combinatorial strategies enable unbiased and model-free approaches to probe sequence/structure relationships. Through the use of combinatorial methods, it is possible (i) to probe the sequence determinants of natural amyloid proteins by screening libraries of amino acid substitutions (mutations) to identify those that prevent amyloid formation; and (ii) to test new hypotheses about the mechanism of formation of amyloid fibrils by using these hypotheses to guide the design of combinatorial libraries of de novo amyloid-like proteins. Here, we review how these two approaches have been used to study the molecular determinants of protein aggregation and amyloidogenicity.

Original languageEnglish (US)
Pages (from-to)279-286
Number of pages8
JournalProtein and Peptide Letters
Volume13
Issue number3
DOIs
StatePublished - Mar 1 2006

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Biochemistry

Keywords

  • Amyloid
  • Combinatorial libraries
  • Protein aggregation
  • Protein design

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